Extramedullary Infiltration in Pediatric Acute Myeloid Leukemia on Surveillance Magnetic Resonance Imaging and its Relationship With Established Risk Factors

Abstract

Purpose: Extramedullary infiltration (EMI) is a rare condition defined by the accumulation of myeloid tumor cells beyond the bone marrow. The clinical significance is still controversial. This study was aimed to evaluate the incidence, characteristics, and prognostic significance of EMI on complete magnetic resonance imaging (MRI) investigation in newly diagnosed pediatric acute myeloid leukemia (AML) patients who are asymptomatic without clinical evidence to suspect EMI.Materials and Methods: Retrospective clinical and radiologic review of 121 patients with MRI examination at the time of initial diagnosis of AML without any clinical evidence suggestive of EMI was performed. Patients were divided into 2 groups according to the presence or absence of EMI, and the relationship between EMI and established risk factors was analyzed. Initial white blood cell count, the occurrence of an event (including relapse, death, and primary refractory disease), survival status, and detailed information on cytogenetic/molecular status was performed by a thorough review of electronic medical records system. All patients underwent full imaging evaluation with the contrast-enhanced whole body and some regional MRI at the time of initial diagnosis. Results:The median age at diagnosis was 10.77 years (range, 0.37 to 18.83 y). Based on the risk stratification system of AML, 36, 45, and 40 patients are classified as low-risk, intermediate-risk, and high-risk groups, respectively. MRI at the time of the initial diagnosis of AML revealed 35 of 121 patients (28.9%) with EMI. The most common site of EMI was a skull, followed by the lower extremity bone and meninges of the brain. The median age at diagnosis was significantly younger in patients with EMI (7.87 vs. 11.08 y, P = 0.0212). Low incidence of FLT3/ITD mutation, low incidence of AML-ETO gene rearrangement, and the larger extent and more severe degree of bone marrow involvement was related with EMI. However, there was no significant prognostic difference in eventfree survival and overall survival regardless of the presence of EMI in the overall patient population and each risk group. The location of EMI occurrence was also not related to prognosis.Conclusions: Even if EMI symptoms are not evident, surveillance MRI scans at the initial diagnosis of pediatric AML patients are very helpful in detecting a significant number of EMIs. Younger age, some molecular features, and more severe bone marrow involvement of AML patients were related with EMI. However, there was no significant prognostic difference between patients with or without EMI regardless of risk group. Further prospective investigation is necessary to validate the prognostic effect of EMI in a larger group of patients with different risk groups.

Genetic alterations in myeloid sarcoma among acute myeloid leukemia patients: insights from 37 cohort studies and a meta-analysis

“…Among them, the FLT3-ITD mutation was the most prevalent, with a pooled prevalence of 17.50% (95% CI 12.60% to 22.50%; I² 82.48%; Figure 2A) (12, 16, 21, 26, 27, 29-34, 36-38, 42, 44-46, 48, 50). Similarly, the MLL and NPM1 mutations stood out with a prevalence of 17.30% (95% CI -7.40% to 42.0%; I² 98.06%; Figure 2C) (9,22,46) and 17.10% (95% CI 11.60% to 22.60%; I² 93.64%; Figure 2B) (9, 12, 15, 16, 23, 24, 26, 27, 29, 31-37, 39-42, 46), respectively. Additionally, the DNMT3A mutation was observed at a prevalence of 16.10% (95% CI 7.80% to 24.30%; I² 80.7%; Figure 2D) (12,27,28,32,36,40,42,50), while the TET2 mutation had a prevalence of 15.40% (95% CI 12.30% to 18.50%; I² 0%; Figure 2E) (12,15,27,36,40,43,47,49,50).…”

“…The KMT2A:: MLLT3 fusion gene was also identified at a pooled prevalence of 19.20% (95% CI -14.60% to 53.00%; I² 79.63%; Figure 3B) (14,43). Furthermore, the CBFB::MYH11 fusion gene was observed at a pooled prevalence of 10.30% (95% CI 5.40% to 15.10%; I² 84.93%; Figure 3C) (9,14,16,24,28,35,38,39,42,45,46,49,50).…”

“…Several noteworthy findings emerged after analyzing gene mutations in patients with MS and non-MS (Figure 4). Specifically, the prevalence of the CEBPA mutation was significantly higher in non-MS patients than in those with MS, with an OR of 0.51 (95% CI 0.32 to 0.81; I² 0%; Figure 4C) (10,35,37,46,50). Conversely, the NRAS mutation was notably more prevalent in the MS group, with an OR of 5.07 (95% CI 1.87 to 13.73; I² 0%; Figure 4G) (31,50).…”

“…Furthermore, we calculated the overall pooled prevalence of AML patients with MS harboring recurrent genetic abnormalities, as per the 2022 World Health Organization classification, to be 36.80% (95% CI: 26.00% to 47.60%; I² 96.85%; Supplementary Data 4) (9, 12, 14-16, 23-29, [31][32][33][34][35][36][37][38][39][40][41][42][43][45][46][47][48][49][50].…”

Successful Treatment of Pediatric Acute Myeloid Leukemia Presenting with Hyperbilirubinemia Secondary to Myeloid Sarcoma: A Case Report

“…Old studies published had variable outcomes due to inclusion of CNS leukemia with MS in the analysis [ 26 , 27 ]. Kim et al and Stove et al reported no significant difference in event free survival (EFS) and overall survival (OS) regardless of the presence or absence of MS [ 28 , 29 ]. A study from India reported the EFS and OS were better in patients with AML and MS compared to those with AML without MS, and the six patients with isolated MS had 100% EFS and OS [ 30 ].…”